DEVELOPMENT AND APPLICATION OF A HIERARCHICAL PROTOCOL FOR AB INITIO PREDICTION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Most of current research in computational biology and bioinformatics is focused on predicting the three-dimensional structure of proteins. Using different approaches, researchers are trying to develop methodology for predicting protein structure based only on amino acid sequence. However, three-dimensional structure alone is not sufficient to understand many biochemical processes which involve proteins. Research presented in this proposal is based on parameterization of our physics-based coarse-grained force-filed UNRES , using information not only about the three-dimensional structure of native state of proteins but also about their folding mechanism and thermodynamic stability. We expect that such parameterization and extensive conformational space search using molecular dynamics will enable us to simultaneously predict two protein properties: structure and thermodynamic stability of the native state and folding pathway(s) which lead from the unfolded to the folded state.